Our goal is to identify the importance of environmental factors to the development of non-insulin dependent diabetes mellitus (NIDDM) and obesity in Pima Indians. We propose to compare Pimas living in Arizona in an affluent environment (data already available) to Pimas living under markedly contrasting conditions in a remote, mountainous region of Northwest Mexico. Also, the comparison of Pima and non-Pima Mexicans will provide further information on two groups genetically unrelated but living in the same environment. The Pimas of Arizona have the highest reported prevalences of NIDDM and obesity. They have been the focus of intensive investigation and a great deal is known about their history. The Arizona Pimas and their ancestors were skilled farmers with extensive knowledge of irrigation, using the water of the Gila River to cover their food needs. At the turn of the century, water became scarce due to diversion upstream by White settlers. The Pimas were forced to curtail farming and experienced a dramatic change in lifestyle which impacted both food intake and physical activity. Subsequently, chronic medical problems such as diabetes and obesity developed. Our preliminary studies of Pimas living in an undeveloped environment in Northwest Mexico indicate their lifestyle is characterized by greater energy expenditure in physical labor and a traditional Mexican diet. We found significant differences between Mexican and Arizona Pimas with respect to body mass index, body composition, and serum cholesterol. In addition, preliminary results suggest NIDDM is less prevalent in the Mexican Pimas. Therefore, we propose to perform measurements of glucose tolerance, hemoglobin A(1c), insulin, and anthropometrics. The genetic distance between Pimas of Mexico and Arizona will be assessed using DNA typing. Lifestyle factors (diet and physical activity), energy metabolism (resting metabolic rate and total energy expenditure), and cardiovascular disease risk factors will be examined as possible determinants of differences observed between the two groups of Mexicans and the Arizona Pimas with respect to the prevalence and complications of NIDDM and obesity. These data will contribute important information regarding the impact of environment on the pathogenesis of NIDDM and obesity.